1. Introduction
Cell culture environment, which includes homogeneity of nutrients and metabolic wastes, as well as exchange efficiency of dissolved gases, significantly affects cell growth and target protein productivity. Although higher mixing speed might maintain homogeneity and efficiency in cell culture, it generates a destructive shear stress on the cells. Classical small-scale culture systems, such as planar apparatus (e.g., culture plates and T-flasks) or shaker flasks (e.g., Erlenmeyer flasks), have several drawbacks regarding cell production yield, with limited scalability, and lack of control on culture parameters (Birch, 1990; Steiner, 2010; Abecasis, 2017). Various bioreactor designs are currently available for cell culture, namely the perfusion bioreactor (Serra, 2010; Simao, 2016; Bancroft, 2003), rotating wall bioreactor (Radtke, 2012; Navran, 2008), and spinner flask bioreactor (Ismadi, 2014; Gupta, 2016). Optimizing the culture conditions in a bioreactor has been an important technical factor to achieve large cell numbers as required for therapeutic purposes (Serra, 2012; Abecasis, 2017; Martin, 2004; Kropp, 2016). The spinner flask bioreactor is the most commonly used type for suspension culture owing to its easy setup and availability. However, there are some difficulties in the design and setup of a generic bioreactor for a wide range of cell types.
Turning or rotary paddles, which enable quick exchange of dissolved air, is also a common suspension culture system. Faster stirring improves the efficiency of mixing, although the shear stress increases, resulting in cell damage (Rawat, 2016). However, if stirring is slowed down, the efficiency of mixing decreases, and uniformity of the culture medium may be lost. Optimal culture conditions are required for balancing the outcome. For large-scale industrial production, energy saving features need to be considered in addition, based on stirring power.
A culture bioreactor, with a new stirring concept (reciprocal motion), has been developed recently (Fig. 1). The culture medium is stirred by an elliptic horizontal plate moving up and down. According to the scale of culture, one elliptic plate, or two elliptic plates with a 90-degree shift may be installed in the bioreactor. For a bioreactor, sealing is an important consideration. A rubber board or bellow-like pipe was designed to seal the bioreactor with reciprocal mixing (Fig.1C). In this report, we aimed to discuss the availability and advantages of the new-concept bioreactor for animal cell culture, comparing it with the conventional bioreactor with rotary paddles.